Acetic Acid → (2R, 3S)-3-Benzyloxy-2-[(4-ethyl-2,3-dioxopiperazin-1-yl)carbonylamino]butyric acid

HRID 64761Notes

Reaction equation

HRID 64761 reaction equation
[CH2:1]([O:8][C@@H:9]([CH3:15])[C@H:10]([C:12]([OH:14])=[O:13])[NH2:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:16]([N:18]1[CH2:23][CH2:22][N:21]([C:24](Cl)=[O:25])[C:20](=[O:27])[C:19]1=[O:28])[CH3:17].CO.C(O)(=O)C>O.CC(C)=O.C(Cl)(Cl)Cl>[CH2:1]([O:8][C@@H:9]([CH3:15])[C@@H:10]([NH:11][C:24]([N:21]1[CH2:22][CH2:23][N:18]([CH2:16][CH3:17])[C:19](=[O:28])[C:20]1=[O:27])=[O:25])[C:12]([OH:14])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 887MethanolHCID 1088134-Ethyl-2,3-dioxopiperazinecarbonyl chlorideHCID 22869571O-Benzyl-D-threonine

Product 1

HCID 56624685(2R, 3S)-3-Benzyloxy-2-[(4-ethyl-2,3-dioxopiperazin-1-yl)carbonylamino]butyric acid

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 6212ChloroformSolvent

Conditions

Temperature
0 °C

Procedure

O-Benzyl-D-threonine (0.92 g, 4.4 mmole) (prepared by the method of T. Mizoguchi, G. Levin, D. W. Woolley, and J. M. Stewart, J. Org. Chem., 1968, 33, 903, who described the L-isomer) was suspended in water (20 ml) and the pH adjusted to 9.5 , giving a virtually complete solution. This was cooled to 0° C. and stirred while 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (1.00 g, 4.9 m mole) in AR acetone (10 ml) was added dropwise. The pH was kept at 9.5 by the addition of further base while the solution was allowed to regain room temperature. After 2 h the solution was acidified to pH 2 and the bulk of the acetone removed by evaporation. The oily product was extracted into ethyl acetate (3×50 ml), then the total organic phase was washed once with brine and dried over sodium sulphate. Evaporation gave the title acid (1.36 g, 82%) as a colourless non-crystalline foam which retained solvent traces tenaciously; Rf 0.35 in chloroform:methanol:acetic acid, 17:2:1; δ(CDCl3) 0.75-1.35 (5H, m, CH3CH and NCH2CH3), 3.1-3.7 (4H, m, 2 NCH2), 3.9-4.25 (2H, m, NCH2), 4.50 (2H, m, CH--CH), 6.25 (1H, brs, D2O exch, OH), 7.25 (5H, s, aryl), 9.50 (1H, brd), J 7 Hz, D2O exch, NH), 9.70 (1H, brs, D2O exch, CO2H).

Workup

  1. customgiving a virtually complete solution
  2. additionwas added dropwise
  3. additionThe pH was kept at 9.5 by the addition of further base while the solution
  4. customto regain room temperature
  5. customthe bulk of the acetone removed by evaporation
  6. extractionThe oily product was extracted into ethyl acetate (3×50 ml)
  7. washthe total organic phase was washed once with brine
  8. dry with materialdried over sodium sulphate
  9. customEvaporation
  10. customgave the title acid (1.36 g, 82%) as a colourless non-crystalline foam which

Sources & evidence

ORD record
ord-f93372bc37bc4fb7b57e864a1433b923
Source dataset
uspto-grants-1986_09
Patent number
US04609652

Reaction notes

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